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Technical Briefs |
1
Department of Chemical Pathology and
2
Twin Research Unit, The Guy’s, King’s College and St. Thomas’ Medical and Dental School, St. Thomas’ Campus, London, United Kingdom SE1 7EH
a author for
correspondence: fax 44-20-7-928-4226, e-mail r.swaminathan{at}kcl.ac.uk
Serum creatinine is widely used as an index of glomerular filtration rate (GFR) (1). However, it is not a sensitive index because GFR may have to decrease by >50% before serum creatinine becomes "abnormal", and this may be at least partly attributable to the wide reference interval for serum creatinine (44–124 µmol/L). One of the factors influencing the creatinine concentration is said to be muscle mass (1)(2). Thus, it can be argued that if the reference interval for serum creatinine can be adjusted for muscle mass, serum creatinine may be a better index of GFR. However, there is little information on the relationship between muscle mass and serum creatinine. We previously have shown that the contribution of lean body mass (LBM) to the variation in serum creatinine in healthy subjects is small (3). In this report, we extend these observations to another group and used a more precise method to measure LBM.
We studied 664 female subjects (age range, 19–76 years) who attended the Twin Research Unit as part of a larger study. Of these, 346 were monozygotic and 318 were dizygotic twins. Body composition (total fat mass and LBM) was determined by dual energy x-ray absorptiometry using a QDR 2000 scanner (Hologic). The long-term imprecision with this scanner is 2%. Fasting blood samples were obtained from all subjects, and serum creatinine was measured by an enzymatic method on a dry chemistry analyzer (Vitros 950; Johnson & Johnson Diagnostic). The CV of the method is 3% at a concentration of 120 µmol/L.
The age, height, weight, total fat mass, LBM, and serum urea and
creatinine values for the group are shown in Table 1
. Simple correlation analysis with correction for the dependency
between observation of twin pairs (using the Generalised Estimating
Equation) showed that serum creatinine was correlated significantly
with LBM (r = 0.171; P <0.0001), percentage
of body fat (r = -0.10; P = 0.011),
and age (r = 0.152; P <0.0001) but not with
body mass index or total fat mass. When stepwise multiple regression
analysis was done using serum creatinine as the dependent variable, and
age, percentage of fat, and LBM as independent variables, the
contributions of LBM, age, and percentage of fat to the variation of
the serum creatinine were 2.9%, 2.1%, and 0.9%, respectively. To
exclude the contribution of genetic influences, the analysis was done
with one of the twins, and the contributions for LBM, age, and fat were
3.8%, 1.9%, and 2.1%, respectively.
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Creatinine is produced nonenzymatically in the skeletal muscle, and the amount of creatinine production, and therefore the 24 h excretion of creatinine, is directly related to muscle mass (4). This relationship has been used to predict muscle mass from creatinine excretion (5)(6). In estimating GFR from serum creatinine, body weight is included in the formula (7) or nomogram (8) to allow for variation in creatinine excretion.
When interpreting serum creatinine, it is believed that LBM should be taken into account (1). However, as shown here and previously (3), the contribution of LBM to variations in serum creatinine is small. The group of subjects studied were all females, and this may account for the low contribution. However, their LBM covered a wide range (23.0–53.7 kg), and thus it is likely that the findings here would be widely applicable.
These results suggest that although creatinine production increases with increasing LBM, there is a concomitant increase in the volume of distribution of creatinine, thereby reducing the relationship between serum creatinine and LBM. Total body water is related to LBM, and Shutte et al. (9) have shown that LBM and total plasma creatinine (plasma volume x creatinine concentration) are well correlated.
We conclude that the contribution of LBM to serum creatinine is small and that correction of serum creatinine according to LBM is unlikely to improve the usefulness of this measurement.
References
The following articles in journals at HighWire Press have cited this article:
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  J. H. Macdonald, S. M. Marcora, M. Jibani, G. Roberts, M. J. Kumwenda, R. Glover, J. Barron, and A. B. Lemmey Bioelectrical impedance can be used to predict muscle mass and hence improve estimation of glomerular filtration rate in non-diabetic patients with chronic kidney disease Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3481 - 3487. [Abstract] [Full Text] [PDF]
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 G Banfi, M Del Fabbro, and G Lippi Relation between serum creatinine and body mass index in elite athletes of different sport disciplines * Commentary Br. J. Sports Med., August 1, 2006; 40(8): 675 - 678. [Abstract] [Full Text] [PDF]
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 T. H. Jafar, C. H. Schmid, and A. S. Levey Serum Creatinine as Marker of Kidney Function in South Asians: A Study of Reduced GFR in Adults in Pakistan J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1413 - 1419. [Abstract] [Full Text] [PDF]
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